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Erschienen in: International Journal of Hematology 2/2019

22.05.2019 | Original Article

Impact of chromosomal abnormalities on the efficacy of lenalidomide plus dexamethasone treatment in patients with relapsed/refractory multiple myeloma

verfasst von: Takashi Yoshida, Masaki Ri, Haruna Fujinami, Yoshiko Oshima, Takuto Tachita, Yoshiaki Marumo, Hirokazu Sasaki, Shiori Kinoshita, Haruhito Totani, Tomoko Narita, Ayako Masaki, Asahi Ito, Shigeru Kusumoto, Takashi Ishida, Hirokazu Komatsu, Shinsuke Iida

Erschienen in: International Journal of Hematology | Ausgabe 2/2019

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Abstract

Lenalidomide is an effective therapeutic agent for multiple myeloma (MM). However, its efficacy in the context of chromosomal abnormalities (CA) is poorly understood. We retrospectively analyzed 83 patients with relapsed/refractory (RR) MM, who received lenalidomide plus low-dose dexamethasone (Ld), in the context of CA. The median age and number of prior therapies were 69 and 2, respectively. Three, 11, 45, and 19 patients achieved complete response, very good partial response, partial response, and stable disease, respectively. Median progression-free survival (PFS) and overall survival (OS) were 11.1 and 38.8 months, respectively. Seventy-two patients were evaluated for frequently observed translocations; median PFS was 24.4 months in 20 patients with t(11;14), 13.0 months in 16 patients with t(4;14), and 3.7 months in seven patients with t(14;16). G-banded karyotype analysis detected 11 hypodiploid patients, who had shorter PFS and OS (2.5 and 6.2 months, respectively) compared to others (13.0 and 43.7 months, respectively). Hypodiploid patients showed poor clinical outcome, whereas patients with t(11;14) showed favorable outcome. In summary, the present study presents the clinical impact of chromosomal abnormalities on the outcome of Ld therapy, and contributes to understanding the appropriate choice of lenalidomide-based therapy to achieve effective treatment of RR MM.
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Literatur
1.
Zurück zum Zitat Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.CrossRefPubMedPubMedCentral Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–20.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.CrossRefPubMed Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133–42.CrossRefPubMed
3.
Zurück zum Zitat Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–32.CrossRefPubMed Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123–32.CrossRefPubMed
4.
Zurück zum Zitat Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23:2147–52.CrossRefPubMed Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia. 2009;23:2147–52.CrossRefPubMed
5.
Zurück zum Zitat Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, et al. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myelome experience. J Clin Oncol. 2013;31:2806–9.CrossRefPubMedPubMedCentral Avet-Loiseau H, Hulin C, Campion L, Rodon P, Marit G, Attal M, et al. Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myelome experience. J Clin Oncol. 2013;31:2806–9.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. 2011;117:4696–700.CrossRefPubMedPubMedCentral Munshi NC, Anderson KC, Bergsagel PL, Shaughnessy J, Palumbo A, Durie B, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. 2011;117:4696–700.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Debes-Marun CS, Dewald GW, Bryant S, Picken E, Santana-Davila R, Gonzalez-Paz N, et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia. 2003;17:427–36.CrossRefPubMed Debes-Marun CS, Dewald GW, Bryant S, Picken E, Santana-Davila R, Gonzalez-Paz N, et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia. 2003;17:427–36.CrossRefPubMed
9.
Zurück zum Zitat Fassas AB, Spencer T, Sawyer J, Zangari M, Lee CK, Anaissie E, et al. Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma. Br J Haematol. 2002;118:1041–7.CrossRefPubMed Fassas AB, Spencer T, Sawyer J, Zangari M, Lee CK, Anaissie E, et al. Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma. Br J Haematol. 2002;118:1041–7.CrossRefPubMed
10.
Zurück zum Zitat Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C. Groupe Francais de Cytogenetique H Hypodiploidy is a major prognostic factor in multiple myeloma. Blood. 2001;98:2229–38.CrossRefPubMed Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C. Groupe Francais de Cytogenetique H Hypodiploidy is a major prognostic factor in multiple myeloma. Blood. 2001;98:2229–38.CrossRefPubMed
11.
Zurück zum Zitat Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101:4569–75.CrossRefPubMed Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101:4569–75.CrossRefPubMed
12.
Zurück zum Zitat Klein U, Jauch A, Hielscher T, Hillengass J, Raab MS, Seckinger A, et al. Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer. 2011;117:2136–44.CrossRefPubMed Klein U, Jauch A, Hielscher T, Hillengass J, Raab MS, Seckinger A, et al. Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer. 2011;117:2136–44.CrossRefPubMed
13.
Zurück zum Zitat Sawyer JR. The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet. 2011;204:3–12.CrossRef Sawyer JR. The prognostic significance of cytogenetics and molecular profiling in multiple myeloma. Cancer Genet. 2011;204:3–12.CrossRef
14.
Zurück zum Zitat Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C, et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia. 2010;24:623–8.CrossRefPubMed Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C, et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia. 2010;24:623–8.CrossRefPubMed
15.
Zurück zum Zitat Chang H, Jiang A, Qi C, Trieu Y, Chen C, Reece D. Impact of genomic aberrations including chromosome 1 abnormalities on the outcome of patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Leuk Lymphoma. 2010;51:2084–91.CrossRefPubMed Chang H, Jiang A, Qi C, Trieu Y, Chen C, Reece D. Impact of genomic aberrations including chromosome 1 abnormalities on the outcome of patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Leuk Lymphoma. 2010;51:2084–91.CrossRefPubMed
16.
Zurück zum Zitat Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M, et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia. 2010;24:1769–78.CrossRefPubMed Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M, et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia. 2010;24:1769–78.CrossRefPubMed
17.
Zurück zum Zitat Kim K, Kim SJ, Voelter V, Suh C, Yoon SS, Lee JJ, et al. Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea-experience from 110 patients. Ann Hematol. 2014;93:113–21.CrossRefPubMed Kim K, Kim SJ, Voelter V, Suh C, Yoon SS, Lee JJ, et al. Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea-experience from 110 patients. Ann Hematol. 2014;93:113–21.CrossRefPubMed
18.
Zurück zum Zitat Kuroda J, Kobayashi T, Taniwaki M. Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy. Expert Rev Anticancer Ther. 2015;15:787–804.CrossRefPubMed Kuroda J, Kobayashi T, Taniwaki M. Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy. Expert Rev Anticancer Ther. 2015;15:787–804.CrossRefPubMed
19.
Zurück zum Zitat Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood. 2009;114:522–5.CrossRefPubMed Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood. 2009;114:522–5.CrossRefPubMed
20.
Zurück zum Zitat Narita T, Inagaki A, Kobayashi T, Kuroda Y, Fukushima T, Nezu M, et al. t(14;16)-positive multiple myeloma shows negativity for CD56 expression and unfavorable outcome even in the era of novel drugs. Blood Cancer J. 2015;5:e285.CrossRefPubMedPubMedCentral Narita T, Inagaki A, Kobayashi T, Kuroda Y, Fukushima T, Nezu M, et al. t(14;16)-positive multiple myeloma shows negativity for CD56 expression and unfavorable outcome even in the era of novel drugs. Blood Cancer J. 2015;5:e285.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Suzuki K, Shinagawa A, Uchida T, Taniwaki M, Hirata H, Ishizawa K, et al. Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: a phase II study. Cancer Sci. 2016;107:653–8.CrossRefPubMedPubMedCentral Suzuki K, Shinagawa A, Uchida T, Taniwaki M, Hirata H, Ishizawa K, et al. Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: a phase II study. Cancer Sci. 2016;107:653–8.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.CrossRefPubMed Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412–20.CrossRefPubMed
23.
Zurück zum Zitat Inagaki A, Tajima E, Uranishi M, Totani H, Asao Y, Ogura H, et al. Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma. Leuk Res. 2013;37:1648–55.CrossRefPubMed Inagaki A, Tajima E, Uranishi M, Totani H, Asao Y, Ogura H, et al. Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma. Leuk Res. 2013;37:1648–55.CrossRefPubMed
24.
Zurück zum Zitat Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed
25.
Zurück zum Zitat Avet-Loiseau H, Durie BG, Cavo M, Attal M, Gutierrez N, Haessler J, et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia. 2013;27:711–7.CrossRefPubMed Avet-Loiseau H, Durie BG, Cavo M, Attal M, Gutierrez N, Haessler J, et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia. 2013;27:711–7.CrossRefPubMed
26.
Zurück zum Zitat Usmani SZ, Rodriguez-Otero P, Bhutani M, Mateos MV, Miguel JS. Defining and treating high-risk multiple myeloma. Leukemia. 2015;29:2119–25.CrossRefPubMed Usmani SZ, Rodriguez-Otero P, Bhutani M, Mateos MV, Miguel JS. Defining and treating high-risk multiple myeloma. Leukemia. 2015;29:2119–25.CrossRefPubMed
27.
Zurück zum Zitat Kobayashi T, Kuroda J, Fuchida S, Kaneko H, Yagi H, Shibayama H, et al. Impact of early use of lenalidomide and low-dose dexamethasone on clinical outcomes in patients with relapsed/refractory multiple myeloma. Int J Hematol. 2015;101:37–45.CrossRefPubMed Kobayashi T, Kuroda J, Fuchida S, Kaneko H, Yagi H, Shibayama H, et al. Impact of early use of lenalidomide and low-dose dexamethasone on clinical outcomes in patients with relapsed/refractory multiple myeloma. Int J Hematol. 2015;101:37–45.CrossRefPubMed
28.
Zurück zum Zitat Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343:301–5.CrossRefPubMed Krönke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343:301–5.CrossRefPubMed
29.
Zurück zum Zitat Kriegsmann K, Baertsch MA, Awwad MHS, Merz M, Hose D, Seckinger A, et al. Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients. Blood Cancer J. 2019;9:13.CrossRefPubMedPubMedCentral Kriegsmann K, Baertsch MA, Awwad MHS, Merz M, Hose D, Seckinger A, et al. Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients. Blood Cancer J. 2019;9:13.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Zambello R, Bonaldi L, Berno T, Martines A, Sechettin E, De March E, et al. Cytogenetic impact on lenalidomide treatment in relapsed/refractory multiple myeloma: a real-life evaluation. Clin Lymphoma Myeloma Leuk. 2015;15:592–8.CrossRefPubMed Zambello R, Bonaldi L, Berno T, Martines A, Sechettin E, De March E, et al. Cytogenetic impact on lenalidomide treatment in relapsed/refractory multiple myeloma: a real-life evaluation. Clin Lymphoma Myeloma Leuk. 2015;15:592–8.CrossRefPubMed
31.
Zurück zum Zitat Van Wier S, Braggio E, Baker A, Ahmann G, Levy J, Carpten JD, et al. Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma. Haematologica. 2013;98:1586–92.CrossRefPubMedPubMedCentral Van Wier S, Braggio E, Baker A, Ahmann G, Levy J, Carpten JD, et al. Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma. Haematologica. 2013;98:1586–92.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Lu J, Lu J, Chen W, Huo Y, Huang X, Hou J, et al. Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Blood Cancer J. 2014;4:e239.CrossRefPubMedPubMedCentral Lu J, Lu J, Chen W, Huo Y, Huang X, Hou J, et al. Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Blood Cancer J. 2014;4:e239.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood. 2009;114:522–5.CrossRefPubMed Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood. 2009;114:522–5.CrossRefPubMed
34.
Zurück zum Zitat Thanendrarajan S, Tian E, Qu P, Mathur P, Schinke C, van Rhee F, et al. The level of deletion 17p and bi-allelic inactivation of TP53 has a significant impact on clinical outcome in multiple myeloma. Haematologica. 2017;102:e364–7.CrossRefPubMedPubMedCentral Thanendrarajan S, Tian E, Qu P, Mathur P, Schinke C, van Rhee F, et al. The level of deletion 17p and bi-allelic inactivation of TP53 has a significant impact on clinical outcome in multiple myeloma. Haematologica. 2017;102:e364–7.CrossRefPubMedPubMedCentral
Metadaten
Titel
Impact of chromosomal abnormalities on the efficacy of lenalidomide plus dexamethasone treatment in patients with relapsed/refractory multiple myeloma
verfasst von
Takashi Yoshida
Masaki Ri
Haruna Fujinami
Yoshiko Oshima
Takuto Tachita
Yoshiaki Marumo
Hirokazu Sasaki
Shiori Kinoshita
Haruhito Totani
Tomoko Narita
Ayako Masaki
Asahi Ito
Shigeru Kusumoto
Takashi Ishida
Hirokazu Komatsu
Shinsuke Iida
Publikationsdatum
22.05.2019
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 2/2019
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-019-02669-z

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